Elucidation of the pathology of early brain injury after subarachnoid hemorrhage focusing on epilepsy
| Project/Area Number |
20K17963
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Mie University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | くも膜下出血 / てんかん / 早期脳損傷 / 神経細胞アポトーシス / テネイシンC / SAH / perampanel / NCSz / マウス / 癲癇 |
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| Outline of Research at the Start |
最近、癲癇がくも膜下出血（SAH）の予後不良因子として知られるようになってきた。基礎研究では早期脳損傷と呼ばれるSAH特有の脳障害が予後不良因子として重要視されている。我々は最近、マトリセルラー蛋白の１つであるテネイシンC （TNC）がSAH後の脳において高発現し、早期脳損傷の原因になることを報告した。そこで、SAH後にTNCが誘導され、早期脳損傷が生じ、その結果、癲癇原性獲得に至ると考え、その仮説を証明することを本研究の目的とする。
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| Outline of Final Research Achievements |
Recently, nonconvulsive seizures have become known as a poor prognostic factor for subarachnoid hemorrhage (SAH) after cerebral aneurysmal rupture. In basic research, brain damage peculiar to SAH, called early brain injury, is considered important as a poor prognostic factor. We recently reported that one of the matricellular proteins, tenascin-C (TNC), was highly expressed in the brain after SAH and caused neuronal apoptosis. Neuronal apoptosis is thought to be important both in early brain injury after SAH and in the acquisition of epileptogenicity. In this study, thus we clarified the relationships among neuronal apoptosis, TNC upregulation, and non-convulsive seizures using SAH model mice.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究はマトリセルラー蛋白の１つであるテネイシンCがてんかん原性獲得において重要な役割を果たす可能性を初めて示した。テネイシンCは病的状態でその発現は誘導され、受容体やサイトカイン、他の細胞外マトリックス蛋白などと反応し、細胞間や、細胞と細胞外マトリックス間の様々な機能を調整することから近年、注目されてきた。テネイシンCを介する新しいてんかん誘発性細胞死のシグナル経路を解明した本研究の成果は、薬剤抵抗性の側頭葉てんかんなど、他原因のてんかん研究にも応用できる可能性があり、てんかん原性獲得やてんかん誘発性細胞死を未然に防ぐ新しい治療法の開発へと発展していく可能性がある。
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Report
(4 results)
Research Products
(29 results)
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[Journal Article] Plasma SPARC Elevation in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage2023
Author(s)
Nakajima H, Kawakita F, Oinaka H, Suzuki Y, Nampei M, Kitano Y, Nishikawa H, Fujimoto M, Miura Y, Yasuda R, Toma N, Suzuki H; pSEED group
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Journal Title
Neurotherapeutics
Volume: -
Issue: 3
Pages: 779-788
DOI
Related Report
Peer Reviewed
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[Journal Article] Effects of New-Generation Antiepileptic Drug Prophylaxis on Delayed Neurovascular Events After Aneurysmal Subarachnoid Hemorrhage2023
Author(s)
Suzuki H, Miura Y, Yasuda R, Yago T, Mizutani H, Ichikawa T, Miyazaki T, Kitano Y, Nishikawa H, Kawakita F, Fujimoto M, Toma N
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Journal Title
Transl Stroke Res
Volume: -
Issue: 6
Pages: 899-909
DOI
Related Report
Peer Reviewed
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[Presentation] Tenascin-C: A Novel Therapeutic Target in Subarachnoid Hemorrhage2020
Author(s)
Masato Shiba, Masashi Fujimoto, Naoki Toma, Yoichi Miura, Fumihiro Kawakita, Yume Suzuki, Yusuke Kuroda, Munenari Ikezawa, Reona Asada, Hideki Kanamaru, Hidenori Suzuki
Organizer
International Stroke Conference
Related Report
Int'l Joint Research
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